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Figure 3.
(a) Solvent-accessible surfaces for the iNOS (left) and eNOS
(right) active sites colored according to Figure 2. The core of
compound 9 binds closer and more parallel to the heme in eNOS.
In iNOS, side chain rotations of Gln, Arg and Arg388 open the
Gln specificity pocket for binding of the bulky inhibitor tail.
(b) Stereoview of the superimposition of bovine eNOS–compound
9 (yellow) and human iNOS–compound 9 (blue) X-ray structures,
highlighting the cascade of conformational changes of
first-shell and second-shell residues upon inhibitor binding to
iNOS.
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